Significant advances were made in discovering the mechanisms of retrovirus-induced immunosuppression in the Friend virus model. We discovered a new form of retrovirus-induced immunosuppression that was mediated by regulatory T cells. Regulatory T cells were found to be induced by chronic infections and rendered the mice incapable of rejecting certain tumor cell transplants. These findings form a conceptual link between virus-induced immunosuppression and autoimmune diseases. Aslo, these results may have relevance to some types of immunosuppression induced when humans are infected with human immunodeficiency virus. We also made significant advances in elucidating how CD4+ T cells control chronic retroviral infection. Two mechanisms were discovered, direct cytolysis of infected cells, and suppression of virus production by infected cells by secretion of gamma interferon. We also used mice with targeted genetic inactivations to probe the roles of several cytokines in both natural recovery from acute infection and in vaccine induced protection from infection.